Pilot Study Of Allogeneic Peripheral Blood Progenitor Cell Transplantation In Patients With Chemotherapy-Refractory Or Poor-Prognosis Metastatic Breast Cancer
18 Years
60 Years
Female
Breast Cancer
Trial Information
Pilot Study Of Allogeneic Peripheral Blood Progenitor Cell Transplantation In Patients With Chemotherapy-Refractory Or Poor-Prognosis Metastatic Breast Cancer
OBJECTIVES:
Primary
- Determine the toxicity and tolerability of allogeneic peripheral blood stem cell
transplantation after a nonmyeloablative preparative regimen comprising anti-thymocyte
globulin, high-dose melphalan, and fludarabine in women with chemotherapy-refractory or
poor-prognosis metastatic adenocarcinoma of the breast.
- Determine the ability of this preparative regimen to facilitate long-term engraftment
of allogeneic stem cells and lymphocytes in these patients.
- Determine the response in measurable/evaluable disease and its temporal relationship to
the preparative chemotherapy used and to the onset of clinical graft-versus-host
disease (GVHD) in patients treated with this regimen.
Secondary
- Determine the progression-free and overall survival of patients treated with this
regimen.
- Determine the tumor response and its temporal relationship to administration of
high-dose chemotherapy and to the onset of GVHD in patients treated with this regimen.
- Determine the frequency and durability of the induction of full donor chimerism of
lymphocytes in patients treated with this regimen.
OUTLINE: This is a nonrandomized, pilot study.
- Nonmyeloablative preparative regimen: Patients receive fludarabine IV over 30 minutes
on days -8 to -4, anti-thymocyte globulin IV over 4 hours on days -7 to -4, and
high-dose melphalan IV over 30 minutes on days -3 and -2.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV (and
then orally when tolerated) every 12 hours beginning on day -4 and tapered after day 42
(if no GVHD occurs) or after day 90 (if grade I acute GVHD occurs). Patients also
receive methotrexate IV on days 1, 3, and 6.
- Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo
allogeneic PBSCT on day 0. Patients also receive filgrastim (G-CSF) IV or
subcutaneously beginning on day 0 and continuing until blood counts recover.
- Donor lymphocyte infusion (DLI): Patients who show disease progression or fail to
achieve full donor type T-cell chimerism (at least 90% donor derived T-cells) by the
90-day assessment posttransplantation, and have no evidence of active GVHD may receive
DLI. Patients who have unresponsive disease with no active GVHD receive subsequent DLIs
every 6-8 weeks.
Patients are followed at 1, 3, 6, 12, 18, 24, 30, and 36 months.
PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma of the breast
- Metastatic disease
- Meets 1 of the following criteria:
- Chemotherapy-unresponsive disease defined as 1 of the following:
- Less than a partial response to 2 consecutive chemotherapy regimens that
included an anthracycline and a taxane in combination or succession
- Progression of disease during or within 3 months of completion of a taxane,
anthracycline, or platinol-based regimen
- Histologically confirmed tumor involvement on bone marrow biopsy
- Measurable or evaluable disease* defined as the following:
- Bidimensionally reproducible measurable mass by physical examination,
ultrasonography, radiography, CT scan, or MRI
- Evaluable lesions apparent on clinical exam, x-ray, CT scan, or MRI which do not
fit the criteria for measurability (e.g., ill-defined post-surgical masses or
masses assessable in 1 dimension only)
- Elevation of biological markers (e.g., CA 27.29) is considered evaluable
disease NOTE: *Bone lesions or pleural or peritoneal effusion alone are not
considered measurable or evaluable disease
- Appropriate candidate for allogeneic stem cell transplantation
- No active CNS metastases
- Available HLA-identical sibling donor
- 6/6 antigen match
- Donor CD34 cells at least 2 times 10^6/kg recipient weight
- Hormone receptor status:
- Estrogen receptor negative or positive
- Estrogen receptor positive tumors must demonstrate progression on at least
1 hormonal manipulation
PATIENT CHARACTERISTICS:
Age
- 18 to 60
Sex
- Female
Menopausal status
- Not specified
Performance status
- Karnofsky 70-100% OR
- ECOG 0-1
Life expectancy
- Not specified
Hematopoietic
- WBC at least 1,500/mm^3
- Platelet count at least 30,000/mm^3
Hepatic
- Bilirubin less than 3 times normal*
- AST and ALT less than 3 times normal* NOTE: *Unless abnormality due to malignancy
Renal
- Creatinine no greater than 1.6 mg/dL
Cardiovascular
- LVEF greater than 40% by echocardiography or MUGA
- No myocardial infarction within the past 6 months
Pulmonary
- DLCO greater than 40% of predicted
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No serious localized or systemic infection
- No hypersensitivity to E. coli-derived products
- No history of non-breast malignant disease within the past 5 years except completely
excised nonmelanoma skin cancer or carcinoma in situ of the cervix
- No chronic inflammatory disorder requiring concurrent glucocorticosteroids or other
immunosuppressive medication
- No psychological condition or social situation that would preclude study
participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- See Disease Characteristics
Endocrine therapy
- No concurrent glucocorticoids
Radiotherapy
- No prior radiotherapy to an indicator lesion unless the lesion shows evidence of
progression after discontinuation of the therapy
Surgery
- Not specified
Other
- No concurrent immunosuppressive medication
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Outcome Measure:
Toxicity
Safety Issue:
Yes
Principal Investigator
Edward D. Ball, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of California, San Diego
Authority:
United States: Federal Government
Study ID:
CDR0000343758
NCT ID:
NCT00074269
Start Date:
July 2003
Completion Date:
Related Keywords:
- Breast Cancer
- recurrent breast cancer
- stage IV breast cancer
- Breast Neoplasms
Name | Location |
|---|---|
| Rebecca and John Moores UCSD Cancer Center | La Jolla, California 92093-0658 |
